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Change Allows Influenza Virus to Spread in Respiratory Droplets

Avian H9N2 influenza hasn't garnered the attention of H5N1, but it, too, might have the potential to cause a pandemic flu. A new study shows that H9N2 can fairly easily gain the ability to transmit in respiratory droplets, like that from a sneeze. Insights from the study will have profound implications for pandemic flu preparation.

Avian influenza viruses primarily infect birds now, but these
viruses constantly change, or mutate. Future mutations might
render them capable of causing a worldwide flu pandemic. Researchers
have focused much attention on H5N1 because of the human deaths
it's caused. But researchers don't have a very good understanding
of how new pandemic viruses emerge.

H9N2 has become endemic in poultry throughout Europe and Asia
within the past few years. It's also occasionally infected people.
To date, H9N2 infections have typically caused symptoms similar
to a seasonal flu, making them likely to escape the attention
of public health officials. Given ample opportunity to circulate,
exchange genetic material with other viruses and improve its
ability to infect and spread, one of these viruses could unexpectedly
spark a pandemic.

Dr. Daniel R. Perez at the University of Maryland and his colleagues
have been studying avian H9N2 viruses in ferrets, which are considered
the gold standard influenza animal model. The team previously
showed when an avian H9N2 virus and a human virus exchanged genetic
material, a resulting "reassortant" virus could replicate
and transmit more effectively than the parent H9N2 virus. This
virus however, didn't transmit through respiratory droplets,
the main mode of influenza transmission in ferrets.

The researchers set out to determine whether the reassortant
virus could gain this ability. Their investigation, funded by
NIH's National Institute of Allergy and Infectious Diseases (NIAID),
the Centers for Disease Control and Prevention and the U.S. Department
of Agriculture, appeared in the online edition of Proceedings
of the National Academy of Sciences on April 20, 2009.

The researchers infected ferrets through their noses, then collected
nasal washes 3 days later, pooled the washes and used them to
infect other ferrets. After passing the virus through ferrets
10 times, the scientists discovered that the viruses spread to
other ferrets through respiratory droplets by 4 days after infection.

Sequencing of the viruses revealed that 3 amino acid changes
on virus surface proteins—2 in the hemaglutinin protein
(the "H" of the virus's name) and 1 in the neuraminidase protein
(the "N")—were responsible for enabling respiratory droplet
transmission. Importantly, one of these changes is located near
a part of the HA protein that scientists have been targeting
for potential vaccines. Antibodies that recognize this region
in other H9N2 viruses, the researchers found, reacted poorly
against the new reassortant virus.

This study suggests that avian H9N2 viruses require little adaptation
to gain the ability to spread through respiratory droplets. The
crucial changes the researchers pinpointed may prompt a rethinking
of how to develop vaccines for a potential pandemic.